Chronic hepatitis B virus (HBV) infection is a significant global health problem, affecting over 5% of the world population (over 350 million people worldwide and 1.25 million individuals in the U.S.).
Despite the availability of a prophylactic HBV vaccine, the burden of chronic HBV infection continues to be a significant unmet worldwide medical problem, due to suboptimal treatment options and sustained rates of new infections in most parts of the developing world. Current treatments rarely provide a cure and are limited to only two classes of agents (interferon and nucleoside analogues/inhibitors of the viral polymerase); drug resistance, low cure rates, and tolerability issues limit their impact. The low cure rates of HBV can be attributed at least in part to incomplete suppression of HBV replication and to the presence and persistence of covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. However, persistent suppression of HBV DNA slows liver disease progression and helps to prevent hepatocellular carcinoma. Therefore, current therapy goals for HBV-infected patients are directed to reducing serum HBV DNA to low or undetectable levels, and to ultimately reducing or preventing the development of cirrhosis and hepatocellular carcinoma.
Although there is precedent for improved efficacy from combination regimens in other viral diseases such as HIV and HCV, combination of existing HBV drugs have failed to show improved efficacy. Neither the combinations of interferon α (IFN) and nucleos(t)ide polymerase inhibitors nor combinations of nucleos(t)ide polymerase inhibitors have provided improved efficacy in treating HBV compared to monotherapy.
Therefore, there remains a need in the art for improved therapies for treating HBV infection.